Evolutionary approaches to autism- an overview and integration

Autism is a highly heritable neurodevelopmental disorder, which greatly reduces reproductive success. The combination of high heritability and low reproductive success raises an evolutionary question: why was autism not eliminated by natural selection? We review different perspectives on the evolution of autism and propose an integration which emphasizes epistatic interactions between the effects of genes during development. It is well-established that autism is a polygenic disorder, and that the genes contributing to autism interact. If a disorder is polygenic, it is likely that the genes underlying the disorder are also involved in traits that are beneficial for the individual. For example, it is possible that genes involved in the development of autism are also involved in the development of intelligence. As intelligence is positively correlated with reproductive success, genes involved in autism can possibly spread in the population. We propose that in most individuals, the interactions between genes result in normal or high intelligence and the absence of autism. However, in some unlucky situations, often in combination with spontaneous negative mutations, the interactions between genes can lead to the development of autism (or other pathologies). Thus, the combination of high heritability and low reproductive success in autism can be explained from an evolutionary developmental perspective that emphasizes the role of epistatic interactions in polygenic disorders

Sexual Dimorphism in the Prenatal Digit Ratio (2D:4D)

The second to fourth digit ratio (2D:4D) is smaller in human males than in females and hence this trait is sexually dimorphic. The digit ratio is thought to be established during early prenatal development under the influence of prenatal sex hormones. However, the general assumption of early establishment has hardly been studied. In our study, we analyzed the 2D:4D ratio in 327 deceased human fetuses. We measured digit lengths in 169 male and 158 female fetuses ranging from 14 to 42 weeks old. Our results showed a slight, but significant, sexual dimorphism in the expected direction, i.e., females had, on average, a ratio of 0.924 and males a ratio of 0.916. There was no significant relationship with the presence or absence of minor and major or single and multiple congenital abnormalities. There was a minimal, but significant difference between digit ratios based on digit lengths including and excluding the non-bony fingertip with the values being strongly correlated (r = .98). The prenatal 2D:4D ratio was lower than has thus far been reported for children and adults both for males and females. The extent of the sexual dimorphism in fetuses was similar to that found for children, but lower than for adults. The 2D:4D ratio, thus, seems to increase after birth in both men and women, with the second digit growing faster than the fourth digit (positive allometric growth of digit two) and perhaps more so in women than in men. Therefore, the sexual dimorphism is probably determined by prenatal as well as by postnatal developmental processes

Breaking evolutionary and pleiotropic constraints in mammals: On sloths, manatees and homeotic mutations

<p>Abstract</p> <p>Background</p> <p>Mammals as a rule have seven cervical vertebrae, except for sloths and manatees. Bateson proposed that the change in the number of cervical vertebrae in sloths is due to homeotic transformations. A recent hypothesis proposes that the number of cervical vertebrae in sloths is unchanged and that instead the derived pattern is due to abnormal primaxial/abaxial patterning.</p> <p>Results</p> <p>We test the detailed predictions derived from both hypotheses for the skeletal patterns in sloths and manatees for both hypotheses. We find strong support for Bateson's homeosis hypothesis. The observed vertebral and rib patterns cannot be explained by changes in primaxial/abaxial patterning. Vertebral patterns in sloths and manatees are similar to those in mice and humans with abnormal numbers of cervical vertebrae: incomplete and asymmetric homeotic transformations are common and associated with skeletal abnormalities. In sloths the homeotic vertebral shift involves a large part of the vertebral column. As such, similarity is greatest with mice mutant for genes upstream of <it>Hox</it>.</p> <p>Conclusions</p> <p>We found no skeletal abnormalities in specimens of sister taxa with a normal number of cervical vertebrae. However, we always found such abnormalities in conspecifics with an abnormal number, as in many of the investigated dugongs. These findings strongly support the hypothesis that the evolutionary constraints on changes of the number of cervical vertebrae in mammals is due to deleterious pleitropic effects. We hypothesize that in sloths and manatees low metabolic and activity rates severely reduce the usual stabilizing selection, allowing the breaking of the pleiotropic constraints. This probably also applies to dugongs, although to a lesser extent.</p

Amniotic fluid deficiency and congenital abnormalities both influence fluctuating asymmetry in developing limbs of human deceased fetuses

Fluctuating asymmetry (FA), as an indirect measure of developmental instability (DI), has been intensively studied for associations with stress and fitness. Patterns, however, appear heterogeneous and the underlying causes remain largely unknown. One aspect that has received relatively little attention in the literature is the consequence of direct mechanical effects on asymmetries. The crucial prerequisite for FA to reflect DI is that environmental conditions on both sides should be identical. This condition may be violated during early human development if amniotic fluid volume is deficient, as the resulting mechanical pressures may increase asymmetries. Indeed, we showed that limb bones of deceased human fetuses exhibited increased asymmetry, when there was not sufficient amniotic fluid (and, thus, space) in the uterine cavity. As amniotic fluid deficiency is known to cause substantial asymmetries and abnormal limb development, these subtle asymmetries are probably at least in part caused by the mechanical pressures. On the other hand, deficiencies in amniotic fluid volume are known to be associated with other congenital abnormalities that may disturb DI. More specifically, urogenital abnormalities can directly affect/reduce amniotic fluid volume. We disentangled the direct mechanical effects on FA from the indirect effects of urogenital abnormalities, the latter presumably representing DI. We discovered that both factors contributed significantly to the increase in FA. However, the direct mechanical effect of uterine pressure, albeit statistically significant, appeared less important than the effects of urogenital abnormalities, with an effect size only two-third as large. We, thus, conclude that correcting for the relevant direct factors allowed for a representative test of the association between DI and stress, and confirmed that fetuses form a suitable model system to increase our understanding in patterns of FA and symmetry development.Research Fund of the University of Antwerp, mobility grant from the Research Foundation – Flanders (FWO)

Homeotic transformations and number changes in the vertebral column of Triturus newts

We explored intraspecific variation in vertebral formulae, more specifically the variation in the number of thoracic vertebrae and frequencies of transitional sacral vertebrae in Triturus newts (Caudata: Salamandridae). Within salamandrid salamanders this monophyletic group shows the highest disparity in the number of thoracic vertebrae and considerable intraspecific variation in the number of thoracic vertebrae. Triturus species also differ in their ecological preferences, from predominantly terrestrial to largely aquatic. Following Geoffroy St. Hilaire's and Darwin's rule which states that structures with a large number of serially homologous repetitive elements are more variable than structures with smaller numbers, we hypothesized that the variation in vertebral formulae increases in more elongated species with a larger number of thoracic vertebrae. We furthermore hypothesized that the frequency of transitional vertebrae will be correlated with the variation in the number of thoracic vertebrae within the species. We also investigated potential effects of species hybridization on the vertebral formula. The proportion of individuals with a number of thoracic vertebrae different from the modal number and the range of variation in number of vertebrae significantly increased in species with a larger number of thoracic vertebrae. Contrary to our expectation, the frequencies of transitional vertebrae were not correlated with frequencies of change in the complete vertebrae number. The frequency of transitional sacral vertebra in hybrids did not significantly differ from that of the parental species. Such a pattern could be a result of selection pressure against transitional vertebrae and/or a bias towards the development of full vertebrae numbers. Although our data indicate relaxed selection for vertebral count changes in more elongated, aquatic species, more data on different selective pressures in species with different numbers of vertebrae in the two contrasting, terrestrial and aquatic environments are needed to test for causality.Serbian Ministry of Education and Science {[}173043]; SyntheSys {[}NL-TAF 1245, NL-TAF 3082]; Naturalis Biodiversity Center `Temminck fellowship

Changes of Fluctuating Asymmetry with Age in Human Fetuses and Young Infants

(1) Background: Developmental instability (DI), often measured by fluctuating asymmetry (FA), increases with stress in humans, yet little is known about how stress affects the changes of asymmetry with age. More specifically, it is unknown if fetuses experiencing a major congenital abnormality will express higher FA already during early development or only at a later age; (2) Methods: We combine two datasets to study associations between age and asymmetry in human fetuses and young infants. One population consists of fetuses from spontaneous abortions and early deceased infants where many experienced major congenital abnormalities, and a second from elicited abortions for social reasons; (3) Results: While the occurrence of major abnormalities did not seem to affect the way asymmetry decreased with age, differences between the two populations were observed; and (4) Conclusions: In one population where fetuses and young infants deceased of natural causes, asymmetry decreased rapidly until 20 weeks of age and then leveled off. Over the entire timespan (week 15–49), individuals with major congenital abnormalities showed higher FA, suggesting that developmental perturbations increase FA rapidly. In the second, more normal population with abortions solicited for social reasons, the decrease in asymmetry with age was less profound and not statistically significant, calling for further research toward understanding regional differences